A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Keratoconjunctivitis Sicca
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 3
- 主要终点
- Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters
研究概览
简要总结
This is a Phase 2, randomized, double-masked, placebo-controlled, parallel-group study in adult males and females, aged 18 years and over, with a diagnosis of moderate-to-severe keratoconjunctivitis sicca (KCS). Patients will be randomized to receive either CF101 1 mg or matching placebo, given orally every 12 hours (q12h) for 12 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 12-week treatment period, followed by a 2-week follow-up period.
详细描述
At a Screening Visit, patients who provide written informed consent will have screening procedures performed, including a complete medical history, medication history, physical examination, including height, weight, sitting blood pressure, pulse rate and temperature, and clinical laboratory tests. Disease activity will be assessed using tear meniscus (TM) height, tear break-up time (BUT), fluorescein staining (FS), Schirmer test, and the Dry Eye Symptom Score (DESS). Doses of artificial tears must be stable for >2 weeks prior to the Screening Visit.
Eligible patients will begin a 2-week run-in period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for lubricant eye drops. Patients who successfully complete the 2-week run-in period will be randomized to their assigned medication (CF101 1 mg or matching placebo) to be taken orally every q12h for 12 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8 and 12, and at Week 14 for a final follow-up assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18 years of age and over;
- •Have a diagnosis of moderate-to-severe KCS as defined by: (1) Schirmer Test (ST) (without anesthesia) < 7 mm/5 min in either eye; AND (2) Positive FS, defined as a corneal punctate fluorescein staining score of ≥1 in either eye, where 0 = none and 3= severe; AND (3) At least 1 of the following ocular symptoms scored at ≥2, where 0 = none and 4 = very severe/interferes with normal activities: photophobia, blurred vision, foreign body sensation, soreness or pain, itching, burning, dryness;
- •Willing to use no topical ocular treatments except for the unpreserved artificial tears;
- •Doses of unpreserved artificial tears have been stable for >2 weeks prior to Screening Visit;
- •Females of child-bearing potential must have a negative urine pregnancy test at screening and throughout the study, to be eligible for, and continue participation in, the study;
- •Females of child-bearing potential must be willing to use 2 methods of contraception deemed adequate by the Investigator (for example oral contraceptive pills plus a barrier method) to be eligible for, and continue participation in, the study;
- •Ability to complete the study in compliance with the protocol; and
- •Ability to understand and provide written informed consent.
排除标准
- •Has Sjögren's Syndrome with significant systemic non-exocrine gland involvement;
- •Has Stevens-Johnson Syndrome;
- •If KCS is due to rheumatoid arthritis or other autoimmune diseases, patient may not be receiving disease-modifying drugs, including methotrexate and biological agents;
- •Use of systemic immunosuppressive drugs;
- •Use of oral corticosteroids >10 mg prednisone, or equivalent, per day;
- •Use of topical steroids within 2 weeks prior to the Screening Visit and for the duration of the study;
- •Receipt of topical cyclosporine eye drops within 3 months prior to the Screening Visit and for the duration of the trial;
- •Presence of chronic ocular disease other than KCS requiring topical treatment;
- •Presence of post-burn ocular injury;
- •Ocular herpes simplex virus infection;
- •Concomitant use of contact lenses;
- •Persistent intraocular inflammation or infection;
- •Active blepharitis;
- •Recent surgical occlusion of the lacrimal puncta;
- •Subepithelial corneal scarring;
- •Anesthetic or neurotrophic corneas;
- •Hemoglobin level <9.0 gm/L;
- •Platelet count <125,000/mm^3;
- •White blood cell count <3500/mm^3;
- •Serum creatinine level outside the laboratory's normal limits;
- •Liver aminotransferase levels greater than 2 times the laboratory's upper limit of normal;
- •Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the Investigator;
- •History of malignancy within the past 5 years (excluding basal cell carcinoma of the skin);
- •Significant acute or chronic medical, ophthalmic, or psychiatric illness that, in the judgment of the Investigator, could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study;
- •Participation in another investigational drug or vaccine trial concurrently or within 30 days; or
- •Other conditions which would confound the study evaluations or endanger the safety of the patient.
研究组 & 干预措施
CF101 1mg
CF101 1 mg given orally every 12 hours for 12 weeks
干预措施: CF101 (Drug)
Placebo
Placebo given orally every 12 hours for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters
时间窗: 12 weeks
Involved placing a standardized paper tear strip inside the lower eyelid for 5 minutes. The tear strip was then removed and the length of the strip that was wet from tears was measured in millimeters. Change from baseline is calculated. Scores range 0-35 mm, with higher scores indicating more (better) tear production.
Change From Baseline to Week 12 in Tear Break-Up Time (BUT) in Seconds
时间窗: 12 weeks
Time elapsed between a complete blink and the development of the first random dry spot on the tear film as seen under fluorescent light. Change from baseline is calculated. Scores range 0-30 seconds, with higher scores indicating better tear composition and function.
Number of Subjects With >25% Improvement in Fluorescein Staining of the Cornea (FS) at Week 12
时间窗: 12 weeks
Severity of corneal epithelial loss as graded by Fluorescein Staining of the cornea, assessed on a 0-4+ scale with 0 = none and 4+ = severe de-epithelialization (in other words, higher scores indicate worse disease), expressed as number of participants with \>25% improvement at Week 12 relative to baseline.
次要结局
- Change From Baseline to 12 Weeks in Dry Eye Symptom Score (DESS)(12 weeks)
- Change From Baseline to Week 12 in Tear Meniscus (TM) Height(12 weeks)
- Percent Change From Baseline to Week 12 in the Use of Artificial Tears(12 weeks)
- Number of Subjects Experiencing Clinical Success at Week 12(12 weeks)